Smart bag used in sensing physiological and/or physical parameters of bags containing biological substance

ABSTRACT

A cost-effective, single use bag or container is provided for storing biological substances that incorporates on its inner wall an electronic device that is configured to measure physiological and/or physical parameters of the enclosed biological substances, such as source history, identification, demographics, time stamping, temperature, pH, conductivity, glucose, O2, CO2 levels etc. The electronic device of the disclosed bag comprises a sensor configured to measure physiological and/or physical parameters of the biological substances enclosed within the bag, and a radio-frequency (RF) device communicably coupled to the sensor and configured to: (a) acquire from the sensor data associated with the measured parameters, (b) store the acquired sensor data in nonvolatile memory, and (c) communicate the stored data wirelessly to a RF reader.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/502,642, filed on Mar. 7, 2017 and entitled “SMART BAG USED INSENSING PHYSIOLOGICAL AND/OR PHYSICAL PARAMETERS OF BAGS CONTAININGBIOLOGICAL SUBSTANCE,” which claims priority to U.S. ProvisionalApplication No. 62/035,128 entitled “SMART BAG USED IN SENSINGPHYSIOLOGICAL AND/OR PHYSICAL PARAMETERS OF BAGS CONTAINING BIOLOGICALSUBSTANCE,” filed Aug. 8, 2014; claims priority to U.S. ProvisionalApplication No. 62/035,152 entitled “SMART LABEL OR ENCAPSULATED THINCONTAINER USED IN SENSING PHYSIOLOGICAL AND/OR PHYSICAL PARAMETERS OFBAGS CONTAINING BIOLOGICAL SUBSTANCES,” filed Aug. 8, 2014; and claimspriority to U.S. Provisional Application No. 62/035,162 entitled“DEVICES AND METHODS FOR THAWING FROZEN BAGS CONTAINING BIOLOGICALSUBSTANCES USING CONTROLLED HIGH DENSITY DRY HEATING,” filed Aug. 8,2014. Each of the above referenced applications is hereby expresslyincorporated by reference in their entities.

FIELD

The present technology relates generally to the field of devices andmethods used in detecting or monitoring physiological and/or physicalparameters of bags containing biological substances.

BACKGROUND

Plasma, blood, blood products and medication bags are supplied by themillions to many medical facilities for transfusion on a daily basis.These bags are frozen and stored into inventory upon arrival and need tobe thawed to no more than 36.6 C (97.99 F) before transfusion.Currently, these bags are not individually monitored for qualitycontrol. At best, evaluation of their contents is done off-line onsampled quantities. Thus, there am no routine procedures in place thatcan provide real-time information on the physiological and/or physicalparameters of these stored biological substances from freezing to veintransfusion including source history, identification, demographics, timestamping, temperature, pH, conductivity, glucose, O₂, CO₂ levels etc.This situation is problematic because it creates opportunities forerrors that can be harmful to patients.

The quality of frozen transfused materials depends on maintainingcontrol over the thawing process. Underheating the substance may causepatients to experience hypothermia whereas overheating may cause severedamage (denaturation) to proteins and other components, thereby reducingthe quality of the transfused fluid and endangering patients. Withrespect to plasma and glycerolized blood, current thawing devices arebased on heat transfer through water bath or water bladders and are notcapable of accurately detecting or monitoring the true temperature ofplasma and glycerolized blood. Instead, these thawing devices can onlyprovide thawing ambient temperature (i.e. water bath or water bladdertemperature) and rely on a time dimension to ensure that the contents ofthe thawed bag is within the desired temperature range. Thusreproducible and consistent thawing results cannot be achieved withoutaccurate temperature sensing of plasma, whole blood, glycerolized bloodand red blood corpuscles. Consequently, there is a need for proceduresthat monitor the quality of drugs and biological substances during thefreezing to vein transfusion life cycle.

SUMMARY

In one aspect, the present technology provides an enclosure for storingbiological substances comprising a bag including an inner and an outerwall, the inner wall being in contact with biological substances, and anelectronic device attached to the inner wall of the bag, including asensor configured to measure physiological and/or physical parameters ofthe biological substances enclosed within the bag, and a radio-frequency(RF) device communicably coupled to the sensor and configured to: (a)acquire from the sensor data associated with the measured parameters,(b) store the acquired sensor data in nonvolatile memory, and (c)communicate the stored data wirelessly to a RF reader.

In some embodiments, the biological substance is fresh, frozen, stored,or thawed and is selected from the group consisting of: medication,plasma, whole blood, glycerolized blood, and red blood corpuscles(RBCs).

In some embodiments, the physical parameters of the biologicalsubstances include identification, source history, demographic data andtime stamping. In some embodiments, the physiological parameters of thebiological substances include temperature, pH, conductivity, glucose,O₂, CO₂ levels etc.

In some embodiments, the RF device is a radio-frequency identification(RFID) tag. In some embodiments, the RF device includes a wirelessantenna or coil configured to receive power from and communicate with aRF reader. In some embodiments, the RF device includes nonvolatilememory configured to store parameters associated with the enclosed bagcontaining biological substances. In some embodiments, the RF deviceincludes acquisition circuitry configured to acquire from the sensordata associated with the measured parameters. In some embodiments, theRFID tag is passive.

In some embodiments, the sensor is a temperature sensor that measuresthe temperature of the biological substances enclosed within the bag. Insome embodiments, the temperature sensor is a traditional resistancetemperature detector (RTD). In some embodiments, the temperature sensoris a thermistor. In some embodiments, the thermistor is a negativetemperature coefficient (NTC) thermistor. In some embodiments, thebiological substance is fresh, frozen, stored, or thawed and is selectedfrom the group consisting of: medication, plasma, whole blood,glycerolized blood, and RBCs.

In another aspect, the present technology discloses a method fordetecting or monitoring physiological and/or physical parameters ofbiological substances enclosed within a bag during the thawing process,comprising: (a) acquiring data associated with physical and/orphysiological parameters of biological substances enclosed within a bagusing a sensor, (b) storing the acquired sensor data on a RFID tag, and(c) communicating the stored data wirelessly to a RF reader.

In some embodiments, the biological substance is fresh, frozen, stored,or thawed and is selected from the group consisting of: medication,plasma, whole blood, glycerolized blood, and RBCs.

In some embodiments, the physical parameters of the biologicalsubstances include identification, source history, demographic data andtime stamping. In some embodiments, the physiological parameters of thebiological substances include temperature, pH conductivity, glucose, O₂,CO₂ levels etc.

In some embodiments, the sensor is a temperature sensor that measuresthe temperature of the biological substances enclosed within the bag. Insome embodiments, the temperature sensor is a traditional resistancetemperature detector (RTD). In some embodiments, the temperature sensoris a thermistor. In some embodiments, the thermistor is a negativetemperature coefficient (NTC) thermistor. In some embodiments, thebiological substance is fresh, frozen, stored, or thawed and is selectedfrom the group consisting of: medication, plasma, whole blood,glycerolized blood, and RBCs.

In some embodiments, the RFID tag is composed of a printed circuitboard, an integrated circuit (IC) chip, a wireless antenna or coil toreceive power from and communicate with a RF reader, nonvolatile memoryconfigured to store parameters associated with the biological substancesenclosed within the bag, and acquisition circuitry. In some embodiments,the RFID tag is passive.

In another aspect, the present technology discloses a method formonitoring the quality of biological substances enclosed within a bagduring the freezing to vein transfusion life cycle, comprising: (a)acquiring data associated with physical and/or physiological parametersof biological substances enclosed within a bag using a sensor, (b)storing the acquired sensor data on a RFID tag, and (c) communicatingthe stored data wirelessly to a RF reader.

In some embodiments, the sensor is a temperature sensor that measuresthe temperature of the biological substances enclosed within the bag. Insome embodiments, the temperature sensor is a traditional resistancetemperature detector (RTD). In some embodiments, the temperature sensoris a thermistor. In some embodiments, the thermistor is a negativetemperature coefficient (NTC) thermistor. In some embodiments, thebiological substance is fresh, frozen, stored, or thawed and is selectedfrom the group consisting of: medication, plasma, whole blood,glycerolized blood, and RBCs.

In some embodiments, the RFID tag is composed of a printed circuitboard, an IC chip, a wireless antenna or coil to receive power from andcommunicate with a RF reader nonvolatile memory configured to storeparameters associated with the biological substances enclosed within thebag, and acquisition circuitry. In some embodiments, the RFID tag ispassive.

In one aspect, the present technology provides a device attached to anouter wall of a bag containing biological substances and is configuredto measure physiological and/or physical parameters of the bag,comprising a sensor configured to measure physiological and/or physicalparameters of bags containing biological substances and aradio-frequency (RF) device communicably coupled to the sensor andconfigured to: (a) acquire from the sensor data associated with themeasured parameters, (b) store the acquired sensor data in nonvolatilememory, and (c) communicate the stored data wirelessly to a RF reader.

In some embodiments, the biological substance is fresh, frozen, stored,or thawed and is selected from the group consisting of: medication,plasma, whole blood, glycerolized blood, and red blood corpuscles(RBCs).

In some embodiments, the physical parameters of the bags containingbiological substances include identification, source history,demographic data and time stamping. In some embodiments, thephysiological parameter of the bags containing biological substancesincludes temperature.

In some embodiments, the RF device is a radio-frequency identification(RFID) tag. In some embodiments, the RF device includes a wirelessantenna or coil configured to receive power from and communicate with aRF reader. In some embodiments, the RF device includes nonvolatilememory configured to store parameters associated with the enclosed bagcontaining biological substances. In some embodiments, the RF deviceincludes acquisition circuitry configured to acquire from the sensordata associated with the measured parameters. In some embodiments, theRFID tag is passive.

In some embodiments, the sensor is a temperature sensor that measuresthe temperature of the bags containing biological substances. In someembodiments, the temperature sensor is a traditional resistancetemperature detector (RTD). In some embodiments, the temperature sensoris a thermistor. In some embodiments, the thermistor is a negativetemperature coefficient (NTC) thermistor. In some embodiments, thebiological substance is fresh, frozen, stored, or thawed and is selectedfrom the group consisting of: medication, plasma, whole blood,glycerolized blood, and RBCs.

In another aspect, the present technology discloses a method fordetecting or monitoring physiological and/or physical parameters of bagscontaining biological substances during the thawing process, comprising:(a) acquiring data associated with physical and/or physiologicalparameters of bags containing biological substances using a sensor, (b)storing the acquired sensor data on a RFID tag, and (c) communicatingthe stored data wirelessly to a RF reader.

In some embodiments, the biological substance is fresh, frozen, stored,or thawed and is selected from the group consisting of: medication,plasma, whole blood, glycerolized blood, and RBCs.

In some embodiments, the physical parameters of the bags containingbiological substances include identification, source history,demographic data and time stamping. In some embodiments, thephysiological parameter of the bags containing biological substancesincludes temperature.

In some embodiments, the sensor is a temperature sensor that measuresthe temperature of the bags containing biological substances. In someembodiments, the temperature sensor is a traditional resistancetemperature detector (RTD). In some embodiments, the temperature sensoris a thermistor. In some embodiments, the thermistor is a negativetemperature coefficient (NTC) thermistor. In some embodiments, thebiological substance is fresh, frozen, stored, or thawed and is selectedfrom the group consisting of: medication, plasma, whole blood,glycerolized blood, and RBCs.

In some embodiments, the RFID tag is composed of a printed circuitboard, an integrated circuit (IC) chip, a wireless antenna or coil toreceive power from and communicate with a RF reader, nonvolatile memoryconfigured to store parameters associated with the bags containingbiological substances, and acquisition circuitry. In some embodiments,the RFID tag is passive.

In another aspect, the present technology discloses a method formonitoring the quality of biological substances during the freezing tovein transfusion life cycle, comprising: (a) acquiring data associatedwith physical and/or physiological parameters of bags containingbiological substances using a sensor, (b) storing the acquired sensordata on a RFID tag, and (c) communicating the stored data wirelessly toa RF reader.

In some embodiments, the sensor is a temperature sensor that measuresthe temperature of the bags containing biological substances. In someembodiments, the temperature sensor is a traditional resistancetemperature detector (RTD). In some embodiments, the temperature sensoris a thermistor. In some embodiments, the thermistor is a negativetemperature coefficient (NTC) thermistor. In some embodiments, thebiological substance is fresh, frozen, stored, or thawed and is selectedfrom the group consisting of: medication, plasma, whole blood,glycerolized blood, and RBCs.

In some embodiments, the RFID tag is composed of a printed circuitboard, an IC chip, a wireless antenna or coil to receive power from andcommunicate with a RF reader nonvolatile memory configured to storeparameters associated with the bags containing biological substances,and acquisition circuitry. In some embodiments, the RFID tag is passive.

In one aspect, the present technology provides an enclosure for thawingbags containing biological substances comprising an overwrap bag havinghigh thermal conductivity including an inner and an outer wall, and anelectronic device attached to the inner wall of the overwrap bag, theelectronic device configured to come into contact with an enclosed bagcontaining biological substances, including a sensor configured tomeasure physiological and/or physical parameters of the enclosed bagcontaining biological substances, and a radio-frequency (RF) devicecommunicably coupled to the sensor and configured to: (a) acquire fromthe sensor data associated with the measured parameters, (b) store theacquired sensor data in nonvolatile memory, and (c) communicate thestored data wirelessly to a RF reader.

In some embodiments, the biological substance is fresh, frozen, stored,or thawed and is selected from the group consisting of: medication,plasma, whole blood, glycerolized blood, and red blood corpuscles(RBCs).

In some embodiments, the physical parameters of the biologicalsubstances include identification, source history, demographic data andtime stamping. In some embodiments, the physiological parameter of thebiological substances includes temperature.

In some embodiments, the RF device is a radio-frequency identification(RFID) tag. In some embodiments, the RF device includes a wirelessantenna or coil configured to receive power from and communicate with aRF reader. In some embodiments, the RF device includes nonvolatilememory configured to store parameters associated with the enclosed bagcontaining biological substances. In some embodiments, the RF deviceincludes acquisition circuitry configured to acquire from the sensordata associated with the measured parameters. In some embodiments, theRFID tag is passive.

In some embodiments, the sensor is a temperature sensor that measuresthe temperature of the enclosed bag containing biological substances. Insome embodiments, the temperature sensor is a traditional resistancetemperature detector (RTD). In some embodiments, the temperature sensoris a thermistor. In some embodiments, the thermistor is a negativetemperature coefficient (NTC) thermistor. In some embodiments, thebiological substance is fresh, frozen, stored, or thawed and is selectedfrom the group consisting of: medication, plasma, whole blood,glycerolized blood, and RBCs.

In another aspect, the present technology discloses a method fordetecting or monitoring physiological and/or physical parameters of anenclosed bag containing biological substances during the thawingprocess, comprising (a) acquiring data associated with physical and/orphysiological parameters of an enclosed bag containing biologicalsubstances using a sensor, (b) storing the acquired sensor data on aRFID tag, and (c) communicating the stored data wirelessly to a RFreader.

In some embodiments, the biological substance is fresh, frozen, stored,or thawed and is selected from the group consisting of: medication,plasma, whole blood, glycerolized blood, and RBCs.

In some embodiments, the physical parameters of the enclosed bagcontaining biological substances include identification, source history,demographic data and time stamping. In some embodiments, thephysiological parameter of the enclosed bag containing biologicalsubstances includes temperature.

In some embodiments, the sensor is a temperature sensor that measuresthe temperature of the enclosed bag containing biological substances. Insome embodiments, the temperature sensor is a traditional resistancetemperature detector (RTD). In some embodiments, the temperature sensoris a thermistor. In some embodiments, the thermistor is a negativetemperature coefficient (NTC) thermistor. In some embodiments, thebiological substance is fresh, frozen, stored, or thawed and is selectedfrom the group consisting of: medication, plasma, whole blood,glycerolized blood, and RBCs.

In some embodiments, the RFID tag is composed of a printed circuitboard, an integrated circuit (IC) chip, a wireless antenna or coil toreceive power from and communicate with a RF reader, nonvolatile memoryconfigured to store parameters associated with the enclosed bagcontaining biological substances, and acquisition circuitry. In someembodiments, the RFID tag is passive.

In one aspect, the present technology provides an apparatus for drythawing a bag containing biological substances comprising a firstcushion device and a second cushion device each including: (a) aflexible heat conducting sheet configured to make contact with a bagcontaining biological substances, (b) a high density heating elementconfigured to supply thermal energy to the flexible heat conductingsheet, (c) a temperature sensor configured to make contact with andmeasure temperature of the bag, (d) a sonic vibrator assembly configuredto sonically agitate the bag; and (e) a flexible non-heat conductinglayer configured to promote unidirectional heat transfer towards the bagcontaining biological substances, and insulate the sonic vibratorassembly and the temperature sensor from the high density heatingelement; and (f) a heat insulation barrier configured to thermallyisolate the temperature sensor from the flexible heat conducting sheetand the high density heating element, wherein the flexible heatconducting sheet of the first cushion device faces the flexible heatconducting sheet of the second cushion device.

In some embodiments, the apparatus of the present technology furthercomprises an electronic connector configured to supply electricalcurrent to the temperature sensor, and the high density heating element.

In some embodiments, the biological substance is selected from the groupconsisting of: medication, plasma, whole blood, glycerolized blood, andRBCs.

In some embodiments, the heat insulation barrier is composed of materialselected from the group consisting of: polystyrene foam, starch-basedfoams, cellulose, paper, rubber, non-woven material, wood, plastic andtin foil.

In some embodiments, the flexible heat conducting sheet is composed ofsilicon. In some embodiments, the perimeter of the flexible heatconducting sheet is larger than the perimeter of the bag containingbiological substances. In some embodiments, the perimeter of theflexible heat conducting sheet is the same as the perimeter of the bagcontaining biological substances.

In some embodiments, the flexible non-heat conducting layer is composedof material selected from the group consisting of: polystyrene foam,starch-based foams, cellulose, paper, rubber, non-woven material, andplastic.

In some embodiments, the temperature sensor is a traditional resistancetemperature detector (RTD). In some embodiments, the temperature sensoris a thermistor. In other embodiments, the temperature sensor is anegative temperature coefficient (NTC) thermistor. In some embodiments,the temperature sensor communicates the measured temperatures of the bagvia the electronic connector during the thawing process.

In some embodiments, the high density heating element is configured tosupply thermal energy to the flexible heat conducting sheet when poweredwith electrical current. In some embodiments, the high density heatingelement is configured to supply thermal energy that is sufficient toheat a 250-500 ml bag of biological substances with a startingtemperature of −40° C. to 36.6° C. within 10 minutes. In otherembodiments, the high density heating element is configured to supplythermal energy that is sufficient to heat a 250-500 ml bag of biologicalsubstances with a starting temperature of −40° C. to 36.6° C. within 5minutes.

In another aspect, the present technology provides a method for drythawing a bag containing biological substances comprising (a) drivingelectrical current through a high density heating element via anelectronic connector, (b) transferring thermal energy generated by thehigh density heating element to a flexible heat conducting sheet,wherein the flexible heat conducting sheet is configured to diffusethermal energy to a bag containing biological substances, (c) agitatingthe bag to achieve homogenous thawing using low frequency sonicvibrations, (d) measuring temperature of the bag using a temperaturesensor, and (e) communicating the measurements via the electronicconnector.

In some embodiments, the biological substance is selected from the groupconsisting of: medication, plasma, whole blood, glycerolized blood, andRBCs.

In some embodiments, the flexible heat conducting sheet is composed ofsilicon.

In some embodiments, the temperature sensor is a traditional resistancetemperature detector (RTD). In some embodiments, the temperature sensoris a thermistor. In other embodiments, the temperature sensor is anegative temperature coefficient (NTC) thermistor. In some embodiments,the temperature sensor communicates the measured temperatures of the bagvia the electronic connector during the thawing process.

In some embodiments, the high density heating element is configured tosupply thermal energy that is sufficient to heat a 250-500 ml bag ofbiological substances with a starting temperature of −40° C. to 36.6° C.within 10 minutes. In other embodiments, the high density heatingelement is configured to supply thermal energy that is sufficient toheat a 250-500 ml bag of biological substances with a startingtemperature of −40° C. to 36.6° C. within 5 minutes.

In some embodiments, the low frequency sonic vibrations range between 10Hz to 50 Hz.

In one aspect, the present technology provides a computer-controlledapparatus for dry thawing bags containing biological substances,comprising (a) a first thawing chamber including: (i) a first cushiondevice and a second cushion device each including: (A) a flexible heatconducting sheet configured to make contact with a bag containingbiological substances; (B) a high density heating element configured tosupply thermal energy to the flexible heat conducting sheet; (C) atemperature sensor configured to make contact with and measuretemperature of the bag; (D) a sonic vibrator assembly configured tosonically agitate the bag; (E) a flexible non-heat conducting layerconfigured to promote unidirectional heat transfer towards the bagcontaining biological substances, and insulate the sonic vibratorassembly and the temperature sensor from the high density heatingelement; and (F) a heat insulation barrier configured to thermallyisolate the temperature sensor from the flexible heat conducting sheetand the high density heating element, wherein the flexible heatconducting sheet of the first cushion device faces the flexible heatconducting sheet of the second cushion device; and (ii) a radiofrequency (RF) reader configured to wirelessly communicate with aradio-frequency identification device (RFID) tag on the bag; (b) acentral controller configured to receive temperature data from thetemperature sensor and the RF reader data, and control the high densityheating element based on the received temperature data; and (c) a powersupply configured to supply electrical current to the high densityheating element based on control signals received from the centralcontroller.

In some embodiments, the computer-controlled apparatus of the presenttechnology further includes a plurality of thawing chambers identical tothe first thawing chamber, wherein the plurality of thawing chambers arecommunicably coupled to the central controller. In some embodiments, theplurality of thawing chambers are part of the main module of thecomputerized closed-loop dry thawing system. In some embodiments, themain module of the computerized closed-loop dry thawing system has a twochamber configuration. In other embodiments, the main module of thecomputerized closed-loop dry thawing system has a four chamberconfiguration. In another embodiment, the main module of thecomputerized closed-loop dry thawing system has an eight chamberconfiguration.

In some embodiments, the central controller includes an expansion portconfigured to communicably couple with a plurality of auxiliary thawingchambers. In some embodiments, the number of auxiliary thawing chambersis two, four, six, eight, ten, or twelve.

In some embodiments, the bag is an overwrap bag including an inner andan outer wall; and an electronic device attached to the inner wall ofthe overwrap bag. In some embodiments, the electronic device isconfigured to come into contact with an enclosed bag containingbiological substances and includes: (a) a sensor configured to measurephysiological and/or physical parameters of the enclosed bag containingbiological substances; and (b) a radio-frequency (RF) devicecommunicably coupled to the sensor and configured to: (i) acquire fromthe sensor data associated with the measured parameters; (ii) store theacquired sensor data in nonvolatile memory; and (iii) communicate thestored data wirelessly to the RF reader.

In some embodiments, the bag is a container including an inner and anouter wall, the inner wall being in contact with biological substances;and an electronic device attached to the outer wall of the container,including: (a) a sensor configured to measure physiological and/orphysical parameters of the container enclosing the biologicalsubstances; and (b) a radio-frequency (RF) device communicably coupledto the sensor and configured to: (i) acquire from the sensor dataassociated with the measured parameters; (ii) store the acquired sensordata in nonvolatile memory; and (iii) communicate the stored datawirelessly to the RF reader.

In some embodiments, the biological substance is selected from the groupconsisting of: medication, plasma, whole blood, glycerolized blood, andRBCs.

In some embodiments, the physical parameters include identification,source history, demographic data and time stamping. In some embodiments,the physiological parameter of the biological substances includestemperature.

In some embodiments, the RF device is a radio-frequency identification(RFID) tag. In some embodiments, the RF device includes a wirelessantenna or coil configured to receive power from and communicate with aRF reader. In some embodiments, the RF device includes nonvolatilememory configured to store parameters associated with the bag. In someembodiments, the RF device includes acquisition circuitry configured toacquire from the sensor data associated with the measured parameters. Insome embodiments, the RFID tag is passive.

In some embodiments, the flexible non-heat conducting layer is composedof material selected from the group consisting of: polystyrene foam,starch-based foams, cellulose, paper, rubber, non-woven material, andplastic.

In some embodiments, the heat insulation barrier is composed of materialselected from the group consisting of: polystyrene foam, starch-basedfoams, cellulose, paper, rubber, non-woven material, wood, plastic andtin foil.

In some embodiments, the temperature sensor is a traditional resistancetemperature detector (RTD). In some embodiments, the temperature sensoris a thermistor. In other embodiments, the temperature sensor is anegative temperature coefficient (NTC) thermistor.

In another aspect, the present technology discloses a computercontrolled process for dry thawing biological substances comprising: (a)generating heat via a high density heating element, (b) diffusing heatgenerated by the high density heating element to a bag containingbiological substances via a flexible heat conducting sheet, (c)agitating the bag to achieve homogenous thawing using low frequencysonic vibrations, (d) measuring temperature of the bag using atemperature sensor, (e) transmitting data associated with the measuredtemperatures to a central controller via an electrical connector, and(f) receiving, in response to (e), control signals for regulating thegeneration of heat by the high density heating element.

In some embodiments, the computer controlled process of the presenttechnology further comprises (a) measuring temperature of the bag usinga radio-frequency identification device (RFID) tag that is affixed tothe bag, (b) receiving temperature data from a RF reader that isconfigured to wirelessly communicate with the RFID tag, and (c)receiving control signals from the central controller for regulating thehigh density heating element in response to (b).

In some embodiments, the low frequency sonic vibrations range between 10Hz to 50 Hz.

In some embodiments, the biological substance is selected from the groupconsisting of: medication, plasma, whole blood, glycerolized blood, andRBCs.

In some embodiments, the bag is an overwrap bag including an inner andan outer wall; and an electronic device attached to the inner wall ofthe overwrap bag. In some embodiments, the electronic device isconfigured to come into contact with an enclosed bag containingbiological substances and includes: (a) a sensor configured to measurephysiological and/or physical parameters of the enclosed bag containingbiological substances; and (b) a radio-frequency (RF) devicecommunicably coupled to the sensor and configured to: (i) acquire fromthe sensor data associated with the measured parameters; (ii) store theacquired sensor data in nonvolatile memory; and (iii) communicate thestored data wirelessly to the RF reader.

In some embodiments, the bag is a container including an inner and anouter wall, the inner wall being in contact with biological substances;and an electronic device attached to the outer wall of the container,including: (a) a sensor configured to measure physiological and/orphysical parameters of the container enclosing the biologicalsubstances; and (b) a radio-frequency (RF) device communicably coupledto the sensor and configured to: (i) acquire from the sensor dataassociated with the measured parameters; (ii) store the acquired sensordata in nonvolatile memory; and (iii) communicate the stored datawirelessly to the RF reader.

In some embodiments, the physical parameters include identification,source history, demographic data and time stamping. In some embodiments,the physiological parameter of the biological substances includestemperature.

In some embodiments, the RF device is a radio-frequency identification(RFID) tag. In some embodiments, the RF device includes a wirelessantenna or coil configured to receive power from and communicate with aRF reader. In some embodiments, the RF device includes nonvolatilememory configured to store parameters associated with the bag. In someembodiments, the RF device includes acquisition circuitry configured toacquire from the sensor data associated with the measured parameters. Insome embodiments, the RFID tag is passive.

In some embodiments, the heat insulation barrier is composed of materialselected from the group consisting of: polystyrene foam, starch-basedfoams, cellulose, paper, rubber, non-woven material, wood, plastic andtin foil.

In some embodiments, the flexible non-heat conducting layer is composedof material selected from the group consisting of: polystyrene foam,starch-based foams, cellulose, paper, rubber, non-woven material, andplastic.

In some embodiments, the temperature sensor is a traditional resistancetemperature detector (RTD). In some embodiments, the temperature sensoris a thermistor. In other embodiments, the temperature sensor is anegative temperature coefficient (NTC) thermistor.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a smart bag/container assembly.

FIG. 2 shows an example smart bag electronic circuit layer (or PCB).

FIG. 3 shows a Smart label cross-section assembly.

FIG. 4 shows a cross-sectional view of an example smart label printedcircuit board (PCB) including an RFID tag.

FIG. 5 shows an example Smart Overwrap Bag.

FIG. 6 shows an example temperature sensing module that can be includedin an overlap bag, such as the one shown in FIG. 5.

FIG. 7 shows the side view of an example thawing cushion device.

FIG. 8 shows another view of an example cushion device 80.

FIG. 9A shows a radial view of an example Sonic Vibrator Assembly.

FIG. 9B shows a cross-sectional view of an example Sonic VibratorAssembly.

FIG. 10 shows the top view of the dry heat thawing chamber.

FIG. 11 illustrates the side view of the dry heat thawing chamber.

FIG. 12 shows an implementation where a thawing chamber is used to thawa bag without an integrated sensor or RF device.

FIG. 13 is a block diagram of a device comprising two typical dry heatthawing chambers (top view).

FIG. 14 is a block diagram of an expanded device from two to fourthawing chambers (top view).

FIG. 15 shows a schematic of an example resistance temperature detector(RTD).

FIG. 16 shows a schematic of an example nondispersive infrared gassensor.

FIG. 17 shows a schematic of an example chemical based carbon dioxidesensor.

FIG. 18 shows a block diagram of an example closed-loop system.

DETAILED DESCRIPTION

The following description discusses apparatus and methods for drythawing bags containing biological substances. Section A discusses asmart bag for containing the biological substances. Section B discussesa smart-label that can be affixed to a bag containing biologicalsubstances. Section C discusses overwrap bags that can be utilized toenclose other bags containing biological substances. Section C alsodiscusses dry thawing chambers used for thawing bags, and modular drythawing systems including multiple thawing chambers.

A. Smart Bag Radio-Frequency Identification (RFID)

Radio-frequency identification (RFID) is the wireless non-contact use ofradio-frequency electromagnetic fields to transfer data, for thepurposes of automatically identifying and tracking tags attached toobjects.

A RFID system uses tags, or labels attached to the objects to beidentified. These tags contain information that is stored in memory.Two-way radio transmitter-receivers called interrogators or readers senda signal to the tag and read its response. RFID tags can be passive,active or battery-assisted passive. An active tag has an on-boardbattery and periodically transmits its ID signal. A battery-assistedpassive (BAP) has a small battery on board and is activated when in thepresence of a RF reader. A passive tag has no battery and must bepowered by and read at short ranges via magnetic fields (electromagneticinduction) from an external source (i.e., a RF reader antenna). Thesetags then act as a passive transponder to emit microwaves or UHF radiowaves (i.e., electromagnetic radiation at high frequencies), which theRF reader picks up and interprets as meaningful data. Passive tags mustbe illuminated with a power level roughly three magnitudes stronger thanfor signal transmission.

In some implementations, RFID tags can include an integrated circuit(IC) for storing and processing information, modulating and demodulatinga radio-frequency (RF) signal, collecting DC power from the incidentreader signal, and other specialized functions; and an antenna forreceiving and transmitting the signal. The tag's components are enclosedwithin plastic, silicon or glass. The RFID tag includes either achip-wired logic or a programmed or programmable data processor forprocessing the transmission and sensor data, respectively. Tags mayeither be read-only, having a factory-assigned serial number that isused as a key into a database, or may be read/write, whereobject-specific data can be written into the tag by the system user.Field programmable tags may be write-once, read-multiple. Data stored onRFID tags can be changed, updated and locked.

An RFID reader transmits an encoded radio signal to interrogate the tag.The RFID tag receives the message and then responds with itsidentification and other information. Signaling between the reader andthe tag is done in several ways, depending on the frequency band used bythe tag. Tags operating on LF and HF bands are, in terms of radiowavelength, very close to the reader antenna because they are only asmall percentage of a wavelength away. In this near field region, thetag is closely coupled electrically with the transmitter in the reader.The tag can modulate the field produced by the reader by changing theelectrical loading the tag represents. By switching between lower andhigher relative loads, the tag produces a change that the reader candetect.

The RFID tag can be affixed to an object and can be read if passed neara reader, even if it is covered by the object or not visible. The tagcan be read inside a case, carton, box or other container, and unlikebarcodes. RFID tags can be read hundreds at a time. Furthermore, passivetags have low production costs and are manufactured to be disposable,along with the disposable consumer goods on which they are placed.

Temperature Sensors

Temperature sensors are devices used to measure the temperature of amedium by assessing some physical property which changes as a functionof temperature (e.g., volume of a liquid, current through a wire). Acommonly used temperature sensor is the resistance temperature detector(RTD). RTDs provide an electrical means of temperature measurement, andutilize the relationship between electrical resistance and temperature,which may be linear or nonlinear.

FIG. 15 shows a schematic of an example resistance temperature detector.As shown in FIG. 19, the RTD contains an outer sheath to preventcontamination from the surrounding medium. This sheath can be composedof material that efficiently conducts heat to the resistor, but resistsdegradation from heat or the surrounding medium. There are severalcategories of RTD sensors, such as, but not limited to: carbonresistors, film thermometers, wire-wound thermometers and coil elements.Sensors are most commonly composed of metals, such as platinum, nickel,or copper. The material chosen for the sensor determines the range oftemperatures in which the RTD could be used. For example, platinumsensors, the most common type of resistor, have a range of approximately−200° C. to 800° C. Connected to the sensor are two insulated connectionleads. These leads continue to complete the resistor circuit.

In some implementations, thermistors can be utilized as a temperaturesensor. Thermistors can use a semiconductor, ceramic or polymer sensor,and can operate based upon the relationship between electricalresistance or these materials and the temperature. In someimplementations, thermistors can exhibit high thermal sensitivity.Thermistors can be classified into two types: a positive temperaturecoefficient (PTC) thermistor, where the resistance increases withincreasing temperature and a negative temperature coefficient (NTC)thermistor, where the resistance decreases with increasing temperature.

NTC thermistors are used mostly in temperature sensing and are made froma pressed disc, rod, plate, bead or cast chip of a semiconductor such asa sintered metal oxide. They work because raising the temperature of asemiconductor increases the number of active charge carriers in theconduction band. The more charge carriers that are available, the morecurrent a material can conduct. The measurable electrical current can besent to the microcontroller via a sensor interface circuitry. Themicrocontroller can process the received temperature readings intodigital signals or values. The microcontroller may store and/or transmitthese digital signals or values.

pH Sensors

A pH sensor is a device that measures the concentration of hydrogen ionsin an aqueous solution. A liquid would be classified as acidic, alkalineor neutral according to its pH value. A pH measurement loop is made upof three components: the pH sensor; a preamplifier; and an analyzer ortransmitter. A pH sensor is a potentiometric or electrochemical sensorthat has a voltage output and consists of a measuring (glass) electrode,a reference electrode and a temperature sensor. The measuring electrode,which is sensitive to the presence of hydrogen ions, develops apotential (voltage) directly related to the hydrogen ion concentrationof the solution. The reference electrode provides a stable potentialagainst which the measuring electrode can be compared. When immersed inthe solution, the reference electrode potential does not change with thechanging hydrogen ion concentration. A solution in the referenceelectrode also makes contact with the sample solution and the measuringelectrode through a junction, thereby completing the circuit. Theelectric potential created between the glass electrode, and thereference electrode is a function of the pH value of the measuredsolution. Thus a pH measurement loop is essentially a battery where thepositive terminal is the measuring electrode and the negative terminalis the reference electrode.

The pH sensor components are usually combined into one device called acombination pH electrode. The measuring electrode is usually glass.Recent developments have replaced glass with more durable solid-statesensors. Additionally, the output of the measuring electrode changeswith temperature even though the process remains at a constant pH. Thusa temperature sensor is necessary to correct for this change in output,and such calibration is accomplished via the analyzer or transmittersoftware. The preamplifier is a signal-conditioning device which takesthe high-impedance pH electrode signal and changes it into a lowimpedance signal which the analyzer or transmitter can accept. Thepreamplifier also strengthens and stabilizes the signal, making it lesssusceptible to electrical noise. The sensor's electrical signal is thendisplayed via an analyzer or transmitter. The measurable electricalcurrent can be sent to a microcontroller via a sensor interfacecircuitry. The microcontroller can process the received pH readings intodigital signals or values. The microcontroller may store and/or transmitthese digital signals or values. Additionally, the analyzer ortransmitter can include a man-machine interface for calibrating thesensor and configuring outputs and alarms, if the pH is being regulated.

Glucose Sensors

A glucose sensor is a device that measures the approximate concentrationof glucose in a blood sample. A consumable element containing chemicalsthat react with blood glucose is used for each measurement. In someimplementations, this element is a plastic test strip with a smallspot(s) impregnated with glucose oxidase, which catalyzes the oxidationof glucose to gluconolactone. In other implementations, the consumableelement is a plastic test strip with a small spot(s) impregnated withglucose dehydrogenase (GDH), which oxidizes D-glucose toD-glucono-1,5-lactone.

In some implementations, the glucose sensors use an electrochemicalmethod. Test strips contain a capillary that retrieves a reproducibleamount of blood. The glucose in the blood reacts with an enzymeelectrode containing glucose oxidase (or glucose dehydrogenase). Theenzyme is reoxidized with an excess of a mediator reagent, such as aferricyanide ion, a ferrocene derivative or osmium bipyridyl complex.The mediator in turn is reoxidized by reaction at the electrode, whichgenerates an electrical current. The total charge passing through theelectrode is proportional to the amount of glucose in the blood that hasreacted with the enzyme. Some sensors employ the coulometric methodwhich measures the total amount of charge generated by the glucoseoxidation reaction over a period of time. Other glucose sensors use theamperometric method which measures the electrical current generated at aspecific point in time by the glucose reaction. Both methods give anestimation of the concentration of glucose in the initial blood sample.The measurable electrical current can be sent to the microcontroller viaa sensor interface circuitry. The microcontroller can process thereceived glucose levels into digital signals or values. Themicrocontroller may store and/or transmit these digital signals orvalues.

CO₂ Sensors

A CO₂ sensor is a device that measures the concentration of carbondioxide gas. Most CO₂ sensors fall into one of two categories:nondispersive infrared gas sensors (NDIR) and chemical based gassensors.

FIG. 16 shows a schematic of an example nondispersive infrared gassensor. NDIR sensors are spectroscopic sensors used to detect CO₂ in agaseous environment. These types of sensors consist of a tube or achamber in which a source of infrared light is placed at one end and adetector at the other end. CO₂ gas is pumped or diffuses into the tubeand the source directs the infrared waves of light in the tube filledwith gas. The carbon dioxide molecules absorb light of a particularwavelength. An optical filter which is placed immediately in front ofthe detector absorbs the light except for the wavelength of lightabsorbed by carbon dioxide molecules. The difference between the amountof Infrared light at the source and the detector is measured by theelectronics. This difference is directly proportional to the number ofcarbon dioxide molecules present in the gas. The microcontroller canprocess the received CO₂ levels into digital signals or values. Themicrocontroller may store and/or transmit these digital signals orvalues. NDIR CO₂ sensors can also be used for detecting dissolved CO₂ bycoupling them to an ATR (attenuated total reflection) optic andmeasuring the gas in situ.

FIG. 17 shows a schematic of an example chemical based carbon dioxidesensor. The basic principle of chemical based carbon dioxide sensors isthe measurement of the pH change of the electrolyte solution caused bythe hydrolysis of the CO₂. The chemical based sensor consists of anoxide electrode, a reference electrode, a bicarbonate-based internalelectrolyte solution, and a gas permeable membrane at the bottom of thesensor. The CO₂ molecules present in the solution diffuse through thegas permeable membrane and enter into the internal electrolyte solution.The carbon dioxide molecules react with the water to form carbonic acid,which again breaks into bicarbonate and proton ions.

CO₂(aq)+H₂O↔H₂CO₃↔HCO₃ ⁻+H⁺

These proton ions decrease the pH of the electrolyte solution, which isdetected by the internal electrodes. The number of proton ions isdirectly proportional to the number of carbon dioxide molecules present.The measurable electrical current can be sent to the microcontroller viaa sensor interface circuitry. The microcontroller can process thereceived CO₂ levels into digital signals or values. The microcontrollermay store and/or transmit these digital signals or values.

O₂ Sensors

An O₂ sensor is a device that measures the concentration of oxygen inthe gas or liquid being analyzed. The Clark-type electrode is the mostused oxygen sensor for measuring oxygen dissolved in a liquid. The basicprinciple is that there is a cathode and an anode submersed in anelectrolyte. Oxygen enters the sensor through a permeable membrane(e.g., Teflon) by diffusion, and is reduced at the cathode, creating ameasurable electrical current. The relationship between the oxygenconcentration and the electrical current is linear. The measurableelectrical current can be sent to the microcontroller via a sensorinterface circuitry. The microcontroller can process the received O₂levels into digital signals or values. The microcontroller may storeand/or transmit these digital signals or values.

Conductivity Sensors

An electrical conductivity sensor is a device that measures the abilityof a solution to transfer (conduct) electric current. Conductivity isthe reciprocal of electrical resistivity (ohms) and is therefore used tomeasure the concentration of dissolved solids which have been ionized ina polar solution.

In some implementations, conductivity sensors employ a potentiometricmethod which is based on induction. The potentiometric method employsfour concentrically arranged electrodes: the outer two rings apply analternating voltage and induce a current loop in the solution while theinner rings measure the voltage drop induced by the current loop. Thismeasurement is directly dependent upon the conductivity of the solution.A shield around the rings maintains a constant field by fixing thevolume of solution around the rings. In some embodiments, the electrodesare cylindrical and made of platinum metal. In other embodiments, theelectrodes are made of stainless steel. While conductivity couldtheoretically be determined using the distance between the electrodesand their surface area using Ohm's law, a calibration using electrolytesof well-known conductivity is usually performed.

Another method of conductivity measurement uses an inductive method,sometimes referred to as a toroidal sensor. The sensor looks like adonut (toroid) on a stick and uses two toroidal transformers which areinductively coupled side by side and encased in a plastic sheath. Acontroller supplies a high frequency reference voltage to the firsttoroid or drive coil which generates a strong magnetic field. As theliquid containing conductive ions passes through the hole of the sensor,it acts as a one turn secondary winding. The passage of this fluid theninduces a current proportional to the voltage induced by the magneticfield. The conductance of the one turn winding is measured according toOhm's law. The conductance is proportional to the specific conductivityof the fluid and a constant factor determined by the geometry andinstallation of the sensor. The second toroid or receiving coil is alsoaffected by the passage of the fluid in a similar fashion. The liquidpassing through the second toroid also acts as a liquid turn or primarywinding in the second toroidal transformer. The current generated by thefluid creates a magnetic field in the second toroid. The induced currentfrom the receiving coil is measured as the output of the sensor. Thecontroller converts the signal from the sensor to specific conductivityof the process liquid. The measurable electrical current can be sent tothe microcontroller via a sensor interface circuitry. Themicrocontroller can process the received electrical conductivity intodigital signals or values. The microcontroller may store and/or transmitthese digital signals or values.

Hermetic Seals

Hermeticity is the process by which the internal environment of thecritical components is made secure from invasion and contamination fromthe external environment, and is a function of both the bulkpermeability of the chosen materials and the seal quality. The degreeand measure of hermeticity is a function of materials choice, final sealdesign, fabrication processes and practices, and the use environment.

The choice of enclosures can span a large range of materials and involvenumerous joining processes. Materials include metals such as nitinol,platinum, or MP35N or other stainless steels, and thin layers of metalssuch as nickel, gold, and aluminum. Other materials may include glass,ceramics (Al₂O₃), conductive epoxies, conformal coatings, silicones.Teflon and many plastics—for example, polyurethanes, silicones, andperfluorinated polymers. Similarly, joining processes vary from the useof adhesive sealants and encapsulants to fusion methods such aslaser-beam welding or reflow soldering, or solid-state processes such asdiffusion bonding. Plastics and laminates can be joined by a variety ofmethods including but not limited to impulse, heated-platen,radio-frequency (RF), dielectric, and ultrasonic sealing.

Smart Bag

FIG. 1 shows a smart bag/container assembly 10. The smart bag 1 includesa smart bag body 1, a smart bag cover 2, a smart bag inlet 2 a, anelectronic circuit layer 4 and a nonconductive heat-isolation layer 5.In some embodiments, the Smart bag or container 1 of the presenttechnology can be soft, semi-rigid or rigid and can be made frommaterials such as plastic, metal thin sheet, or other materials and/or acombination thereof. In some embodiments, the cover 2 of the Smart bagor container is hermetically sealed to protect its contents 3. In someembodiments, the hermetic seal is composed of biologically inertmaterial (e.g., epoxy). In some embodiments, the hermetically sealedcover 2 of the Smart bag or container contains an inlet 2 a, wherein theinlet can be a valve, mechanical stopper, a spigot, or a plug. FIG. 1shows an implementation where the cover 2 of the Smart bag 10 containsan inlet 2 a. The inlet 2 a ensures the sterile transfer of biologicalsubstances into and out of the Smart bag 10. In some embodiments, theSmart bag or container 10 is low-cost and disposable after a single use.

The Smart bag 10 can accommodate any volume of biological substances andcan function in a wide ambient temperature range (−196° C. to +40° C.).In some embodiments, the biological substances are fresh, frozen, storedor thawed and are selected from the group consisting of medication,plasma, whole blood, glycerolized blood, and RBCs. FIG. 1 shows animplementation where a heat-isolation, nonconductive layer 5 can beprinted on specific areas of the inner wall of the Smart bag 10. Asshown in FIG. 1, an RFID tag containing an electronic circuit layer 4(also known as a printed circuit board (PCB)) is printed or glued on theinner side of the heat-isolation, nonconductive layer 5 such that anattached sensor (e.g., temperature sensor, pH sensor, glucose sensor,oxygen sensor, carbon dioxide sensor, conductivity sensor) will befacing the opposite direction and is in direct contact with the fresh,frozen, stored or thawed biological substance 3 contained within the bag10. Biological substances can be selected from the group consisting ofmedication, plasma, whole blood, glycerolized blood, and RBCs. Besidesserving as an attachment site, the heat-isolation, nonconductive layer 5helps reduce the impact of the ambient temperature on the readings ofthe RFID tag. The on-board electronics of the PCB are powered byelectromagnetic induction from a RF reader antenna.

FIG. 2 shows an example smart bag electronic circuit layer (or PCB) 20.As shown in FIG. 2, the PCB layer 20 includes an RFID tag 21communicably coupled to a sensor assembly 25 that can measure thephysiological and/or physical parameters of biological substancescontained within the Smart bag 10 shown in FIG. 1. The RFID tag-sensorcoupling is achieved by integrating electronic components such asuniversal signal acquisition circuits (which read and acquire sensorsdata) on the PCB layer 20.

The PCB layer 20 can further include power interface circuitry 22 a forreceiving power from an RFID reader. In some implementations, the powerinterface circuitry can be coupled to an RF reader antenna 22 andharvest power from the voltage induced in the antenna 22 due to an RFsignal received from the RF reader. In some implementations, the powerinterface circuitry 22 a can include a rectifier for rectifying the A/Cvoltage appearing across the antenna into a D/C voltage. In someimplementations, the power interface circuitry 22 a may also includevoltage step-up and voltage step-down circuitry for providing thedesired voltages to various components on the PCB layer 20. The powerinterface circuitry 22 a can be used to provide power to all the othercircuitry included in the RFID tag 21, for example, the sensors,microcontrollers, memory, any interface circuitry, etc. In someimplementations, the PCB 20 can be coupled to a battery to receive powerin addition to or instead of receiving power as a result of an RF signalreceived from the RF reader.

The PCB 20 can also include a microcontroller or a microprocessor 23 forreceiving and processing the sensor data received from the sensors 25(e.g., temperature sensor, pH sensor, glucose sensor, oxygen sensor,carbon dioxide sensor, conductivity sensor etc., discussed above). Inaddition, the microcontroller 23 can also be utilized for carrying outcommunications with the external RFID reader. In some implementations,the microcontroller 23 can include a memory for storing executableinstructions for processing and storing sensor data, for communicatingwith the external RF reader, etc. In some implementations, the memorycan include nonvolatile memory configured to store sensed parametersassociated with biological substances enclosed within Smart bags, andacquisition circuitry. For example the physiological parameters caninclude temperature, pH, conductivity, glucose, O₂, and CO₂ levels andthe physical parameters can include identification, source history,demographic data and time stamping. In some implementations, themicrocontroller or microprocessor 23 can be implemented using FPGAs(field-programmable gate arrays) or ASICs (application-specificintegrated circuits).

A sensor interface circuitry 24 can be provided for the microcontroller23 to interface with the sensor 25. In some implementations, the sensorinterface circuitry 24 can include an analog-to-digital converter (ADC)for converting analog voltages/currents (representing the measuredparameter) output by the sensor 25 into digital data. Such digital datacan then be processed, stored, and/or transmitted by the microcontroller23. In some implementations, the sensor interface circuitry 24 can beincluded within the microcontroller 23 itself.

During its operation, the RFID tag 21 stores the acquired sensor data innonvolatile memory and communicates the stored data wirelessly to a RFreader. For instance, in one embodiment, the electronic device of theSmart bag can include thermistors and/or other temperature sensors(e.g., traditional RTDs) that contact and measure the temperature of thebiological substances enclosed within the bag during the thawingprocess. The RFID tag 21 of the Smart bag will then store thetemperature data associated with the enclosed biological substances innonvolatile memory and will wirelessly communicate the stored data to aRF reader. Furthermore, because the RFID tag 21 facilitates accuratetemperature sensing of the enclosed biological substances, the dangersof overheating and/or underheating during the thawing process areminimized. In some embodiments, the temperature sensor is a traditionalresistance temperature detector (RTD). In some embodiments, thetemperature sensor is a thermistor. In some embodiments, the thermistoris a negative temperature coefficient (NTC) thermistor.

In some embodiments, the sensor assembly 25 can include a pH sensor thatmeasures the pH of the biological substances enclosed within the bag. Insome embodiments, the sensor assembly 25 can include a glucose sensorthat measures the glucose levels of the biological substances enclosedwithin the bag. In some embodiments, the glucose sensor uses glucoseoxidase as the consumable element for each measurement. In someembodiments, the glucose sensor uses glucose dehydrogenase as theconsumable element for each measurement. In some embodiments, theglucose sensor employs the coulometric method. In other embodiments, theglucose sensor employs the amperometric method.

In some embodiments, the sensor assembly 25 can include a CO₂ sensorthat measures the CO₂ levels of the biological substances enclosedwithin the bag. In some embodiments, the CO₂ sensor assembly 25 caninclude a nondispersive infrared gas sensor (NDIR). In some embodiments,the CO₂ sensor is a chemical based gas sensor. In some embodiments, thesensor is an O₂ sensor that measures the O₂ levels of the biologicalsubstances enclosed within the bag. In some embodiments, the O₂ sensoris a Clark-type electrode.

In some embodiments, the sensor assembly 25 can include an electricalconductivity sensor that measures the ability of the biologicalsubstances enclosed within the bag to transfer (conduct) electriccurrent. In some embodiments, the electrical conductivity sensor employsthe potentiometric method. In other embodiments, the electricalconductivity sensor is a toroidal sensor.

B. Smart Label and Encapsulated Thin Container for Smart Bags SmartLabel

As used herein, the term Smart label refers to a device that includesone or more sensors configured to measure parameters of bags containingbiological substances and a radio-frequency (RF) device (i.e., the RFIDtag) communicably coupled to the sensor and configured to: (a) acquirefrom the sensor parameters associated with bags containing biologicalsubstances, (b) store the acquired sensor data in nonvolatile memory,and (c) communicate the stored data wirelessly to a RF reader.

In some embodiments, the label or encapsulated thin container of thepresent technology can be soft, semi-rigid or rigid and can be made frommaterials such as plastic, metal thin sheet, or other materials and/or acombination thereof. In some embodiments, the label is hermeticallysealed. In some embodiments, the hermetic seal can be composed ofbiologically inert material (e.g., epoxy). In some embodiments, thelabel can be low-cost and disposable after a single use.

Hermeticity is the process by which the internal environment of thecritical components is made secure from invasion and contamination fromthe external environment, and is a function of both the bulkpermeability of the chosen materials and the seal quality. The degreeand measure of hermeticity is a function of materials choice, final sealdesign, fabrication processes and practices, and the use environment.

The choice of enclosures can span a large range of materials and involvenumerous joining processes. Materials include metals such as nitinol,platinum, or MP35N or other stainless steels, and thin layers of metalssuch as nickel, gold, and aluminum. Other materials may include glass,ceramics (Al₂O₃), conductive epoxies, conformal coatings, silicones,Teflon and many plastics—for example, polyurethanes, silicones, andperfluorinated polymers. Similarly, joining processes vary from the useof adhesive sealants and encapsulants to fusion methods such aslaser-beam welding or reflow soldering, or solid-state processes such asdiffusion bonding. Plastics and laminates can be joined by a variety ofmethods including but not limited to impulse, heated-platen,radio-frequency (RF), dielectric, and ultrasonic sealing.

The Smart label can function in a wide ambient temperature range (−196°C. to +40° C.). FIG. 3 shows a cross-sectional view of an implementationwhere a Smart label 30 can be affixed to an outer wall of a bag (notshown) containing biological substances. As shown in FIG. 3, an adhesivelayer 36 is located on the same side as a temperature sensor 35. Theadhesive layer 36 allows the smart label 30 to be affixed to the outerwall of the bag. In other implementations, the adhesive layer 36 and thetemperature sensor 35 are located on opposite sides, thus allowing theSmart label 30 to be affixed to the inner wall of a bag containingbiological substances. The bag containing the biological substances canbe of any size. In some embodiments, the biological substances arefresh, frozen, stored or thawed and are selected from the groupconsisting of medication, plasma, whole blood, glycerolized blood, andRBCs.

FIG. 3 shows an implementation where the side of the Smart label 30,which interfaces with the ambient environment, is covered by aheat-isolation, nonconductive layer 32. The heat-isolation,nonconductive layer 32 helps reduce the impact of the ambienttemperature on the readings of the Smart label 30. As shown in FIG. 3,the Smart Label 30 can include an RFID tag composed of a printed circuitboard (PCB) 34 that is printed or glued on the inner side of theheat-isolation, nonconductive layer 32 such that an attached sensor(e.g., temperature sensor) 35 will be facing the opposite direction andis in contact with the bag or enclosure containing the fresh, frozen,stored or thawed biological substance. The biological substances may beselected from the group consisting of medication, plasma, whole blood,glycerolized blood, and RBCs. The on-board electronics 33 of the PCB 34are powered by electromagnetic induction from a RF reader antenna.

FIG. 4 shows a cross-sectional view of an example smart label printedcircuit board (PCB) 40 including an RFID tag 41. The PCB 40 can be usedto implement the PCB 34 shown in FIG. 3. The PCB 40 can be affixed to anouter wall 46 of a bag containing biological substances. In someimplementations, the PCB 40 can be instead affixed to an inner wall ofthe bag. As shown in FIG. 4, the RFID tag 41 is communicably coupled toa sensor 35 (also shown in FIG. 3) that can measure the physiologicaland/or physical parameters of bags containing biological substances. TheRFID tag-sensor coupling is achieved by integrating electroniccomponents such as universal signal acquisition circuits (which read andacquire sensors data) on the PCB layer 40.

The PCB 40 can further include power interface circuitry 42 forreceiving power from an RFID reader. In some implementations, the powerinterface circuitry 42 can be coupled to an RF reader antenna 43 andharvest power from the voltage induced in the antenna due to an RFsignal received from the RF reader. In some implementations, the powerinterface circuitry 42 can include a rectifier for rectifying the A/Cvoltage appearing across the antenna into a D/C voltage. In someimplementations, the power interface circuitry 42 may also includevoltage step-up and voltage step-down circuitry for providing thedesired voltages to various components on the PCB 40. The powerinterface circuitry can be used to provide power to all the othercircuitry included in the RFID tag 41, for example, the sensors,microcontrollers, memory, any interface circuitry, etc. In someimplementations, the PCB 40 can be coupled to a battery to receive powerin addition to or instead of receiving power as a result of an RF signalreceived from the RF reader.

The PCB 40 can also include a microcontroller or a microprocessor 44 forreceiving and processing the sensor data received from the sensors 35(e.g., temperature sensor). In addition, the microcontroller 44 can alsobe utilized for carrying out communications with the external RFIDreader. In some implementations, the microcontroller 44 can include amemory for storing executable instructions for processing and storingsensor data, for communicating with the external RF reader, etc. In someimplementations, the memory can include nonvolatile memory configured tostore sensed parameters associated with bags containing biologicalsubstances, and acquisition circuitry. For example the physiologicalparameters can include temperature and the physical parameters caninclude identification, source history, demographic data and timestamping. In some implementations, the microcontroller or microprocessor44 can be implemented using FPGAs (field-programmable gate arrays) orASICs (application-specific integrated circuit).

A sensor interface circuitry 44 a can be provided for themicrocontroller 44 to interface with the sensor 35. In someimplementations, the sensor interface circuitry 44 a can include ananalog-to-digital converter (ADC) for converting analogvoltages/currents (representing the measured parameter) output by thesensor into digital data. Such digital data can then be processed,stored, and/or transmitted by the microcontroller 44. In someimplementations, the sensor interface circuitry 44 a can be includedwithin the microcontroller 44 itself.

During its operation, the RFID tag 41 stores the acquired sensor data innonvolatile memory and communicates the stored data wirelessly to a RFreader. For instance, in one embodiment, the Smart label comprises ofthermistors and/or other temperature sensors (e.g., traditional RTDs)that contact and measure the temperature of bags containing biologicalsubstances during the thawing process. The RFID tag 41 of the Smartlabel will then store the temperature data associated with the bagscontaining biological substances in nonvolatile memory and willwirelessly communicate the stored data to a RF reader. Because the RFIDtag of the Smart label facilitates accurate temperature sensing of bagscontaining biological substances, the dangers of overheating and/orunderheating during the thawing process are minimized. In someembodiments, the temperature sensor is a traditional resistancetemperature detector (RTD). In some embodiments, the temperature sensoris a thermistor. In some embodiments, the thermistor is a negativetemperature coefficient (NTC) thermistor.

C. Devices and Methods for Thawing Frozen Bags Containing BiologicalSubstances Using Dry Heating Smart Overwrap Bag

FIG. 5 shows and example Smart overwrap bag 50. The Smart overwrap bag50 can be composed of materials having high thermal conductivity such asplastic, metal thin sheet, other known thermal conductors, and/or acombination thereof, and can function in a wide ambient temperaturerange (−196° C. to +40° C.). The Smart overwrap bag 50 can be routinelyused to enclose and protect bags 53 containing biological substancesfrom microbial contamination during the thawing process. In the eventthat the bag 53 containing biological substances leaks or breaks duringthe thawing process, the overwrap bag 50 isolates the biologicalcontents, thereby preventing them from contaminating the thawing deviceor system.

The overwrap bag 50 can enclose a bag containing biological substancesof any size (e.g., 250-500 ml). In some embodiments, the overwrap bag 50can be soft, semi-rigid or rigid and its cover can hermetically sealedto protect its contents. In some embodiments, the hermetic seal iscomposed of biologically inert material (e.g., epoxy). In someembodiments, an engaging mechanism at the opening of the overwrap bag 50may be used to remove the bag containing biological substances after thethawing process is complete. FIG. 5 shows an implementation where theengaging mechanism at the opening of the overwrap bag is a ziplock 52.In some embodiments, the overwrap bag 50 can be low-cost and can bedisposable after a single use.

In some embodiments, the overlap bag 50 can have high thermalconductivity. The high thermal conductivity of the overwrap bag 50 canfacilitate rapid thawing of the enclosed bags 53 containing biologicalsubstances. In some embodiments, a dry thawing method can be used forthawing the enclosed bag 53. In other embodiments, conventionalwater-bath or water bladder methods can also be used. In someembodiments, mechanical agitation can be used during the thawing methodto achieve a homogenous temperature profile within the enclosed bag 53containing biological substances and to prevent damage to the biologicalsubstances. In some embodiments, the biological substances can be fresh,frozen, stored or thawed and can include medication, plasma, wholeblood, glycerolized blood, and RBCs. In some embodiments, the overlapbag 50 can include one or more temperature sensing modules 54 forsensing the temperature of the enclosed bag 53.

FIG. 6 shows an example temperature sensing module 54 that can beincluded in an overlap bag, such as the one shown in FIG. 5. In someimplementations, the temperature sensing module 54 can be similar to theSmart label 30 discussed above in relation to FIG. 3. The temperaturesensing module 54 can include a heat-conductive layer 56, an electroniccircuit 57, and a temperature sensor 58. As shown in FIG. 6, theheat-nonconductive layer 56 can be printed or disposed on specific areasof an inner wall 59 of the overwrap bag. The inner wall 59 of theoverlap bag can also be in contact with the outer wall of the enclosedbag containing biological substances (such as the enclosed bag 53 shownin FIG. 5). According to FIGS. 6 and 7, an RFID tag containing anelectronic circuit layer (or a printed circuit board (PCB)) is printedor glued on the inner side of the heat-nonconductive layer such that anattached sensor (e.g., temperature sensor) will be facing the oppositedirection and is in contact with the bag containing the fresh, frozen,stored or thawed biological substance. Biological substances can beselected from the group consisting of medication, plasma, whole blood,glycerolized blood, and RBCs. Besides serving as an attachment site, theheat-nonconductive layer helps reduce the impact of the ambienttemperature on the readings of the RFID tag. The on-board electronics ofthe PCB are powered by electromagnetic induction from a RF readerantenna. As shown in FIG. 7, the RFID tag is communicably coupled to asensor that will measure the physiological and/or physical parameters ofthe enclosed bags containing biological substances. The RFID tag-sensorcoupling is achieved by integrating electronic components such asuniversal signal acquisitions (which read and acquire sensor data) onthe PCB layer.

The PCB can further include power interface circuitry for receivingpower from the RFID reader. In some implementations, the power interfacecircuitry can be coupled to the RF reader antenna and harvest power fromthe voltage induced in the antenna due to an RF signal received from theRF reader. In some implementations, the power circuitry can include arectifier for rectifying the A/C voltage appearing across the antennainto a D/C voltage. In some implementations, the power circuitry mayalso include voltage step-up and voltage step-down circuitry forproviding the desired voltages to various components on the PCB. Thepower circuitry can be used to provide power to all the other circuitryincluded in the RFID tag, for example, the sensors, microcontrollers,memory, any interface circuitry, etc. In some implementations, the PCBcan be coupled to a battery to receive power in addition to or insteadof receiving power as a result of an RF signal received from the RFreader.

The PCB can also include a microcontroller or a microprocessor forreceiving and processing the sensor data received from the sensors(e.g., temperature sensor). In addition, the microcontroller can also beutilized for carrying out communications with the external RFID reader.In some implementations, the microcontroller can include a memory forstoring executable instructions for processing and storing sensor data,for communicating with the external RF reader, etc. In someimplementations, the memory can include nonvolatile memory configured tostore sensed parameters associated with enclosed bags containingbiological substances during the thawing process, and acquisitioncircuitry. For example the physiological parameters can includetemperature and the physical parameters can include identification,source history, demographic data and time stamping. In someimplementations, the microcontroller or microprocessor can beimplemented using FPGAs (field-programmable gate arrays) or ASICs(application-specific integrated circuits).

A sensor interface circuitry can be provided for the microcontroller tointerface with the sensor. In some implementations, the sensor interfacecircuitry can include an analog-to-digital converter (ADC) forconverting analog voltages/currents (representing the measuredparameter) output by the sensor into digital data. Such digital data canthen be processed, stored, and/or transmitted by the microcontroller. Insome implementations, the sensor interface circuitry can be includedwithin the microcontroller itself.

During its operation, the RFID tag stores the acquired sensor data innonvolatile memory and communicates the stored data wirelessly to a RFreader. For instance, in one embodiment, the electronic device of theoverwrap bag comprises of thermistors and/or other temperature sensors(e.g., traditional RTDs) that contact and measure the temperature ofenclosed bags containing biological substances during the thawingprocess. The RFID tag of the overwrap bag will then store thetemperature data associated with the enclosed bags containing biologicalsubstances in nonvolatile memory and will wirelessly communicate thestored data to a RF reader. Because the RFID tag facilitates accuratetemperature sensing of the enclosed bags containing biologicalsubstances, the dangers of overheating and/or underheating during thethawing process are minimized In some embodiments, the temperaturesensor is a traditional resistance temperature detector (RTD). In someembodiments, the temperature sensor is a thermistor. In someembodiments, the thermistor is a negative temperature coefficient (NTC)thermistor.

In some implementations, the RFID tag may be implemented on asystem-on-chip (SOC). In some other implementations, the RFID tag may beimplemented using discrete components.

In some embodiments, a Smart label, similar to the Smart label 30discussed above in relation to FIG. 3 can be utilized as a sensingmodule within the overlap bag 50 shown in FIG. 5.

Cushion Device

The present technology provides a device and method for thawing bags ofbiological substances without the use of water baths or water bladders.FIG. 7 shows a side view of an example dry thawing cushion device 70. Inparticular, the cushion device includes a flexible non-heat conductinglayer, i.e., the cushion 71 that is affixed to a sonic vibrator assembly76 on its outer side, and a printed circuit board (not shown) on itsinner side. The printed circuit board on the inner side of the cushioninterfaces with a heating element 72 and one or more temperature sensors75. As shown in FIG. 10, the heating element 72 is attached to aflexible heat conducting sheet 73, the flexible heat conducting sheet 73being configured to come into contact with a bag containing biologicalsubstances. Additionally FIG. 10 shows one or more temperature sensors75 placed in or around the center on the inner side of the cushion,which are configured to (a) make contact with the bag in need of thawingand (b) periodically measure the temperature of the bag during thethawing process. In some embodiments, the temperature sensor 75 can be atraditional resistance temperature detector (RTD). In some embodiments,the temperature sensor can be a thermistor. In some embodiments, thethermistor can be a negative temperature coefficient (NTC) thermistor.

In some embodiments, the cushion device 70 can include two cushiondevices facing each other, such that the two cushion devices can thaw abag containing biological substances. The two cushion devices can havedimensions that are configured to contact a standard 250 ml-500 ml bagcontaining medication, plasma, whole blood, glycerolized blood bag, RBCsand/or other biological substances. Additionally, the flexible nature ofthe cushion materials ensure that bags or containers for biologicalsubstances of larger sizes can be accommodated within the space betweenthe two flexible heat conducting sheets of the first and second cushiondevices.

In some embodiments, the cushion 71 can be composed of materials thathave low thermal conductivity, and can include, without limitation,materials such as polystyrene foam, starch-based foams, cellulose,paper, rubber, non-woven material, and plastic. As seen in FIGS. 7 and14, the cushion 71 insulates the sonic vibrator 76 assembly andtemperature sensor 75 from the thermal energy generated by the heatingelement 72. The cushion 71 thus serves a dual purpose: protecting thesonic vibrator assembly 76 and temperature sensor 75 from thermal damageand facilitating efficient unidirectional heat transfer from the heatingelement 72 to the flexible heat conducting sheet 73 to the bag ofbiological substances that requires thawing.

In some embodiments, the heating element 72 located between the cushion71 and the flexible heat conducting sheet 73 is a high density,low-power heating element.

In some embodiments, the flexible heat conducting sheet 73 is thin andcomposed of silicon or other materials with similar thermal conductivityproperties. FIG. 16 shows an implementation where the flexible heatconducting sheet is transparent. In other implementations, the flexibleheat conducting sheet is opaque or translucent.

As shown in FIGS. 7 and 14, the temperature sensor 75 is placed inclearance of the flanking heat element 72 and the flexible heatconducting sheet 73 in order to prevent thermal damage to the sensor 75.As shown in FIG. 7, the temperature sensor 75 can be also mounted on andsurrounded by heat insulation barriers 74 with the above clearancedimensions. The presence of the heat insulation barriers 74 can minimizethe impact of the heating element 72 and flexible heat conducting sheet73 on the temperature sensor 75 readings. In some embodiments, the heatinsulation barriers 74 are composed of materials including, but notlimited to polystyrene foam, starch-based foams, cellulose, paper,rubber, non-woven material, wood, plastic and tin foil.

While mechanical agitation is routinely used to expedite thawing,conventional thawing devices that employ this technique often consist ofmoving components that generate unwanted noise. The sonic vibratorassembly 76 discussed below generates low frequency (10 Hz-50 Hz)vibrations to achieve homogenous thawing within the bag containingbiological substances. These low frequency vibrations are barelyperceptible to the human ear, thereby circumventing the need to useaudible mechanical moving mechanisms that cause noise. As shown in FIG.7, the sonic vibrator assembly 76 is affixed to the outer side of thecushion 71. The sonic vibrator assembly 76 includes, among others, thefollowing components: two electrodes, a piezoceramic disc, and wireleads.

Piezoelectric materials, such as, for example, the piezoceramic disc,have the ability to generate a voltage in response to an appliedmechanical stress or conversely change shape in response to an appliedvoltage. In some implementations, the piezoceramic disc may be composedof high power “hard” materials, high sensitivity “soft” materials, orhigh performance piezoelectric crystals. In some implementations, anexample of which is shown in FIGS. 9A and 9B, the piezoceramic disc 92is sandwiched between two electrodes (91 and 93), and lead wires 94 areattached to each electrode (91 and 93). In some implementations, theelectrodes 91 and 93 are composed of metal. In a further implementation,the electrodes 91 and 93 of the sonic vibration assembly 76 comprise asilver electrode and a brass plate. FIGS. 9A and 9B show animplementation where one side of the piezoceramic disc 92 is adhered toa brass plate electrode 93, while the opposite side of the piezoceramicdisc 92 is adhered to a silver electrode 91. As shown in FIG. 9B, thebrass plate electrode 93 is affixed to the flexible non-heat conductinglayer, i.e. the cushion 95. In some implementations, as shown in FIG.9A, the radius of the brass plate electrode 93 is larger than that ofthe piezoceramic disc 92 and the silver electrode 91.

When an alternating voltage signal with a certain frequency is appliedto the leads 94, the alternating potential difference between the twoelectrodes, namely the silver electrode 91 and the brass plate electrode93, causes the piezoceramic disc 92 to mechanically expand or contractin the radial direction at substantially the same frequency as that ofthe applied alternating voltage signal. This resulting radial expansionand contraction of the piezoceramic disc 92 causes the brass plateelectrode 93 to vibrate with the piezoceramic disc 92. These vibrationsin the brass plate electrode 93 can, in turn, be transferred to thecushion to which the brass plate electrode 93 is adhered. Thus,application of a low frequency alternating signal (e.g., 10 Hz) to thepiezoceramic disk 92 can, in effect, cause the brass plate electrode 93to vibrate at substantially the same low frequency, thereby permitting alow frequency vibrations to propagate through the cushion 95 and createan agitation effect. In some implementations, the thickness of theelectrode that makes contact with the cushion 95 (e.g., the brass plateelectrode 93 in FIG. 9B) can, in part, affect the amplitude of thevibrations transferred to the cushion. In some implementations, thethickness of the brass plate electrode 93 in FIG. 9B ranges from about0.5 mm to about 1 mm. In some implementations, the brass plate electrode93 in FIG. 9B is 0.5 mm thick. In some implementations, the brass plateelectrode 93 in FIG. 9B is 1 mm thick.

The electrical power requirements of the heating element and thetemperature sensor(s) can be supplied via an electronic connector. Forexample, FIG. 8 shows another view of an example cushion device 80. Thecushion device 80 includes a cushion 81, a high density heating element82, a temperature sensor 85 disposed between a heat insulation barrier84. Wires from the high density heating element 82 and the temperaturesensor 95 affixed into an electronic connector 87 that is configured toconnect to a power source (not shown) and a controller (not shown).

Dry Thawing Using the Cushion Device

FIGS. 10 and 11 show a top view and a side view, respectively, of a dryheat thawing chamber 100. The dry heat thawing chamber 100 includes afirst side chamber 101 and an adjustable second side chamber 101 a. Thefirst side chamber 101 includes a first cushion device 103, a firstheating element 102, a first temperature sensor 104, a first sonicvibrator assembly 105, a first heat insulation barrier 107, a first heatconducting sheet 108, and a first radio-frequency (RF) reader 106. Theadjustable second side chamber 101 a includes a second cushion device103 a, a second heating element 102 a, a second temperature sensor 104a, a second sonic vibrator assembly 105 a, a second heat insulationbarrier 107 a, a second heat conducting sheet 108 a, and a second RFreader 106 a. The thawing chamber 100 also includes a front end control(FEC) board 109. FIGS. 10 and 11 also show an overlap bag 110 containingan enclosed bag 111.

As shown in FIGS. 10 and 11, the bag 111 containing medication, plasma,whole blood, glycerolized blood, RBCs or any other biological substanceis placed in the space between the two flexible heat conducting sheets108 and 108 a of the first and second cushion devices 103 and 103 a.When powered with electrical current, the high-density heating elements102 and 102 a produce thermal energy which diffuses into the flexibleheat conducting sheets 108 and 108 a. At the onset of the thawingprocess, heat is transferred from the flexible heat conducting sheets108 and 108 a to the bag 111 in need of thawing by conduction. Thermalconvective flow may take prominence as the biological substance near theheated walls of the bag 111 becomes liquefied. The low frequencyvibrations produced by the sonic vibrator assemblies 105 and 105 aprevent concentration gradients from being formed during the thawingprocess and helps achieve an almost homogenous temperature profilewithin the bag. Additionally, temperature sensors 104 and 104 a measurethe temperature of the bag 111 and communicate the measurements to acontroller via the electronic connector during the thawing process. Thedry thawing process can be terminated as soon as the bag 111 containingthe biological substance reaches a desired temperature, thereby reducingthe risk of overheating, underthawing, and denaturation, and increasingthe efficiency of the thawing process. In some embodiments, a standard250 ml-500 ml bag containing plasma, whole blood, glycerolized bloodbag, and/or other biological substances with a starting temperature of−40° C. can be thawed to 36.6° C. within 10 minutes when the cushiondevice is powered with electrical current. In some embodiments, astandard 250 ml-500 ml bag containing plasma, whole blood, glycerolizedblood bag, and/or other biological substances with a startingtemperature of −40° C. can be thawed to 36.6° C. within 5 minutes whenthe cushion device is powered with electrical current.

The disclosed dry thawing device confers several advantages: (1) reducedrisk of microbial contamination compared to thawing methods involvingwater-baths, (2) uniform thawing of the biological substance resultingin reduced risk of overheating, underthawing or denaturation, (3) lowmaintenance compared to conventional water baths and water bladders.

As shown in FIGS. 10 and 11, the perimeter of the flexible heatconducting sheets 108 and 108 a is larger than the perimeter of the bag111 containing the biological substance. In other embodiments, theperimeter of the flexible heat conducting sheets 108 and 108 a is thesame as the perimeter of the bag 111 containing biological substances.

Dry Heat Thawing Chamber

The present technology discloses an apparatus that implements a modular,computerized, closed-loop dry thawing process and is configured to haveat least two separate thawing chambers. Each thawing chamber is aself-contained unit that can be altered or replaced without affectingthe remainder of the system. FIG. 13 shows a schematic of an examplemodular dry thawing apparatus 130. In particular, FIG. 13 shows a mainmodule 132 including two separate thawing chambers 133. Each thawingchamber 133 can be implemented using the dry heat thawing chamber 100discussed above in relation to FIGS. 10 and 11. The main module 132 alsoincludes a central controller 135, a universal power supply 136, and agraphical user interface or display 137. The central controller 135 caninclude a control program for controlling the thawing chambers 133. Thecentral controller can receive data received from the RF readers andprovide control signals to the thawing chambers 133. The centralcontroller 135 can also include expansion ports 138 for connectingauxiliary modules, and include communication ports 139 for providingcommunication to external devices. The power supply 136 can receive ACpower 136 and provide one or more AC or DC voltages and currents to thevarious components of the main module 132 (and any auxiliary modules).

FIG. 14 shows a schematic of another modular dry thawing apparatus 140including at least two modules: a main module 132 and an auxiliarymodule 132 a. The auxiliary module 132 a can be used as an expansionmodule and connect into and controlled by the main module 132. Theauxiliary module 132 a can allow adding capacity to the modular drythawing apparatus 140.

As shown in FIGS. 13 and 14, individual thawing chambers 133 of the mainmodule 132 or auxiliary module 132 a may be encompassed within theirrespective external enclosures. In some embodiments, the main module 132of the computerized closed-loop dry thawing system 130 has a two chamberconfiguration. In other embodiments, the main module 132 of thecomputerized closed-loop dry thawing system has a four chamberconfiguration. In another embodiment, the main module 132 of thecomputerized closed-loop dry thawing system has an eight chamberconfiguration. Generally, the main module 132 can include any number ofdry heat thawing chambers 133.

As seen in FIG. 14, a thawing chamber 133 is a three-dimensionalrectangular compartment that encloses two dry thawing cushion devices.In some embodiments, the exterior of the thawing chamber is composed ofplastic, metal, or a metal alloy (e.g., stainless steel). In otherembodiments, the thawing chamber has a bacteria-resistant powder coatedexterior. As discussed above, in relation to FIGS. 10 and 11, the drythawing device comprises two cushion devices wherein the heat conductingportion of the first cushion device faces the heat conducting portion ofthe second cushion device. FIG. 14 shows an implementation where one ofthe elongated side walls of the thawing chamber 133 is adjustable. Insuch an implementation, the components of the cushion device (i.e., theflexible non-heat conducting layer, flexible heat conducting sheet,heating element, temperature sensor, sonic vibrator assembly, and heatinsulation barrier) that are contiguous to the adjustable side wall arealso adjustable. This feature permits the flexible heat conductingsheets of the thawing device to properly contact the walls of a bagcontaining biological substances, regardless of the volume of the bag. Adetailed description regarding the structural components of the cushiondevice and its operation is discussed above.

In some embodiments, RF readers are embedded in the interior walls ofthe thawing chamber 133. Fixed RF readers are set up to create aspecific interrogation zone which can be tightly controlled. Here, theinterrogation zone would be the space between the two flexible heatconducting sheets of the first and second cushion devices. Thisdesignated space acts as a repository for bags that incorporate RFIDtags and are used for storing biological substances. This allows ahighly defined reading area for when RFID tags go in and out of theinterrogation zone. The RF readers embedded in the interior walls ofeach thawing chamber serve to (a) power the on-board RFID tags of (i)overwrap bags and (ii) bags containing biological substances with SmartLabels affixed to their outer wall, through electromagnetic inductionfrom the RF reader antenna and (b) wirelessly detect the electromagneticradiation emitted by these RFID tags and interpret these signals asmeaningful data. In some embodiments, the thawing chamber 133 can beused for thawing bags such as the smart bag 10 shown in FIG. 1, theoverwrap bag 50 shown in FIG. 5, and bags having a Smart label discussedabove in relation to FIG. 6.

In some embodiments, the thawing chamber 133 also can be used forthawing bags that lack integrated sensors and/or RF devices. Forexample, FIG. 12 shows an implementation where a thawing chamber 120 isused to thaw a bag 121 without an integrated sensor or RF device. Thebag 120 is placed on a cushion 122 including a high density heatingelement 123. The cushion 122 can be similar to the cushion device 80discussed above in relation to FIG. 8. That is, the cushion 122 caninclude a temperature sensor for sensing the temperature of the bag 120,and an RFID for transmitting the sensed temperature to a RF reader. Insome embodiments, the bag 120 may also be enclosed in an overlap bag,such as the one discussed above in relation to FIG. 5.

In other implementations, the chamber 133 can be used for thawing bagsthat incorporate a sensor configured to measure temperature of the bagand a radio-frequency (RF) device communicably coupled to the sensor andconfigured to: (a) acquire from the sensor data associated with themeasured temperatures, (b) store the acquired sensor data in nonvolatilememory, and (c) communicate the stored temperature data wirelessly to aRF reader (i.e., a Smart Label). One example of such a bag is discussedabove in relation to FIG. 1. In some embodiments, the sensor and the RFdevice are affixed to the outer wall of the bag. In some embodiments,the sensor and the RF device are affixed to the inner wall of the bag.In some embodiments, the sensors and RF devices affixed to the innerwall of the bag sense and store additional physical and physiologicalparameters including source history, identification, demographics, timestamping, temperature, pH, conductivity, glucose, O₂, CO₂ levels, whichcan subsequently be communicated wirelessly to a RF reader.

In some embodiments, the thawing chamber 133 may be used to thaw bagscontaining biological substances that are enclosed and protected byoverwrap bags, one example of which is discussed above in relation toFIG. 5. These overwrap bags incorporate a sensor configured to measuretemperature of the enclosed bags containing biological substances and aradio-frequency device communicably coupled to the sensor and configuredto: (a) acquire from the sensor data associated with the measuredtemperatures, (b) store the acquired sensor data in nonvolatile memory,and (c) communicate the stored temperature data wirelessly to a RFreader.

In some embodiments, each thawing chamber 133 can include a front endcontrol board 134 that permits direct user-interaction with the thawingchamber 133. In some embodiments, the front end control board 134comprises a chamber temperature display, bag temperature display, one ormore timer displays, controls for setting or adjusting chambertemperature, a heating status visual indicator, controls for setting oradjusting sonic vibration parameters, and a power switch. In someimplementations, the sonic vibration controls permit users to manuallyinput the desired frequency (Hz) and timing of the sonic vibratorassembly. In some implementations, the front end control board 134contains controls permitting the user to set a program sequence forsonic vibration and/or temperature modulation. In some implementations,the front end control board 134 contains controls that permit users tomanually start or stop sonic vibration and/or heating at any pointduring the thawing process. In some implementations, the front endcontrol board 134 contains an audiovisual alarm that indicates when thebag temperature reaches the desired temperature (e.g., 36.6° C.).

FIG. 18 shows a block diagram of an example closed-loop system. Aclosed-loop system refers to a system which compares an output variableof a system to a certain reference value and manipulates the inputs of asystem to obtain the desired effect on the output of the system.

The modular dry thawing apparatus 130, and in particular the centralcontroller 135, shown in FIG. 13 can utilize a closed-loop dry thawingmethod. For example, the closed-loop dry thawing method can utilize theexample closed loop system shown in FIG. 18. First, temperature sensorsmonitor the system output (temperature) of a bag containing biologicalsubstances in each thawing chamber 133 and transmit the data to thecentral controller 135. The central controller 135 then transforms thedata and compares it to a preset value, e.g., the desired temperature,and subsequently adjusts the system input (electrical current) asnecessary to thaw the bag and achieve the desired temperature. Thecentral controller affects the temperature of the bag, which in turn ismeasured and looped back to alter the control.

As shown in FIGS. 13 and 14, the universal power supply 136 driveselectrical current to all electrical components of the dry thawingapparatus including the sonic vibrator assembly, the high densityheating filament, and the built-in temperature sensors of the cushiondevice, the RF readers of the thawing chambers 133, the centralcontroller, and the graduated AC/DC power supply. In someimplementations, the universal power supply 136 drives electricalcurrent to the graphic user interface 137.

As shown in FIGS. 13 and 14, the central controller 135 controls allfunctional aspects of the disclosed dry thawing apparatus 130 and 140.The central controller 135 acquires from the temperature sensors of thecushion devices data associated with recurring measured temperatures,transforms and compares the acquired data to the preset temperaturevalue, and generates an error signal by subtracting the sensed valuefrom the preset temperature value. The central controller 135 thenresponds to the generated error signal by regulating the electricalcurrent supplied to the high density heating elements in a particularthawing chamber 133 until the bag achieves the preset temperature value.The central controller 135 can also adjust the electrical currentsupplied to the high density heating elements in a given thawing chamber133 based on input that is manually entered by the user. In someimplementations, user input can be directly entered into the centralcontroller 135. In other implementations, user input can be enteredthrough a remote device that is linked to the central controller 135 viaa LAN/WAN Wifi network 136 a. In some implementations, the centralcontroller 135 communicates with the graduated AC/DC power supply 136 toregulate the electrical current supplied to a thawing chamber 133. Insome implementations, the central controller 135 will automatically shutoff electrical power to flexible heat conducting sheets within aparticular thawing chamber 133 once the bag containing biologicalsubstances reaches the desired temperature. In some implementations, thecentral controller 135 will trigger an audio and/or visual alarm chamberonce the bag containing biological substances reaches the desiredtemperature.

The central controller 135 is also communicably coupled to RF readersthat are embedded in the interior walls of the thawing chamber 133. Thisfeature permits the central controller 135 to read and interpret anydata acquired from RFID tags that are affixed to overwrap bags or bagscontaining biological substances (i.e., bags including Smart Labels) inthe thawing chamber 133. The central controller acquires from the RFreaders data associated with recurring measured temperatures, transformsand compares the acquired data to the preset temperature value, andgenerates an error signal by subtracting the sensed value from thepreset temperature. The central controller then responds to thegenerated error signal by regulating the electrical current supplied tothe high density heating elements in a particular thawing chamber 133until the bag achieves the preset temperature value. The centralcontroller 135 can also adjust the electrical current supplied to thehigh density heating elements in a given thawing chamber 133 based oninput that is manually entered by the user. In some implementations,user input can be directly entered into the central controller 135. Inother implementations, user input can be entered through a remote devicethat is linked to the central controller via a LAN/WAN Wifi network. Insome implementations, the central controller 135 communicates with thegraduated AC/DC power supply 136 to regulate the electrical currentsupplied to a thawing chamber. In some implementations, the centralcontroller 135 will automatically shut off electrical power to flexibleheat conducting sheets within a particular thawing chamber once the bagcontaining biological substances reaches the desired temperature.

The central controller 135 also displays sensor output on a graphic userinterface (GUI) 137. In some embodiments, the GUI 137 is a smart phone,personal digital assistant, a laptop LCD monitor, or a desktop LCDmonitor. Alternatively, the central controller 135 can communicatesensor output wirelessly to a remote device using a LAN/WAN WiFinetwork.

Expansion ports 138 add functionality to a computer system via acollection of wires and protocols. As shown in FIG. 14, the computerizedclosed-loop system utilizes an expansion port 138, which facilitatesmovement of information between the central controller 135 and auxiliarythawing chambers 133 in the auxiliary module 132 a that are separate anddistinct from the main module 132 of the dry thawing apparatus 140. As aresult, the central controller 135 can monitor and regulate theauxiliary thawing chambers 133 in a manner identical to that of thethawing chambers 133 within the main module 132 of the dry thawingapparatus. In some embodiments, the expansion port 138 is a serial port.In some embodiments, the expansion port 138 is selected from the groupconsisting of: serial port, parallel port, USB port and multi-LO cards.In some embodiments, the auxiliary module 132 a of the computerizedclosed-loop dry thawing system 140 has a two chamber configuration. Insome embodiments, the auxiliary module 132 a of the computerizedclosed-loop dry thawing system has a four chamber configuration. In someembodiments, the auxiliary module 132 a of the computerized closed-loopdry thawing system has a six chamber configuration. In some embodiments,the auxiliary module 132 a of the computerized closed-loop dry thawingsystem has an eight chamber configuration. In some embodiments, theauxiliary module 132 a of the computerized closed-loop dry thawingsystem has a ten chamber configuration. In some embodiments, theauxiliary module 132 a of the computerized closed-loop dry thawingsystem has a twelve chamber configuration. Generally, the auxiliarymodule 132 a can include any number of dry heat thawing chambers 133 a.

In some implementations, the RFID tag may be implemented on asystem-on-chip (SOC). In some other implementations, the RFID tag may beimplemented using discrete components.

As used herein, the term “about” in reference to a number is generallytaken to include numbers that fall within a range of 5%, 10%, 15%, or20% in either direction (greater than or less than) of the number unlessotherwise stated or otherwise evident from the context.

As used herein, the terms “cushion” and “flexible non-heat conductinglayer” are used interchangeably throughout the specification.

The term “temperature sensing module” refers to an electronic deviceconfigured to come into contact with a bag containing biologicalsubstances, including a sensor configured to measure temperature of thebag containing biological substances, and a radio-frequency (RF) devicecommunicably coupled to the temperature sensor and configured to: (a)acquire from the sensor data associated with the measured temperatures,(b) store the acquired sensor data in nonvolatile memory, and (c)communicate the stored data wirelessly to a RF reader.

The present technology is not to be limited in terms of the particularembodiments described in this application, which are intended as singleillustrations of individual aspects of the present technology. Manymodifications and variations of this present technology can be madewithout departing from its spirit and scope, as will be apparent tothose skilled in the art. Functionally equivalent methods andapparatuses within the scope of the present technology, in addition tothose enumerated herein, will be apparent to those skilled in the artfrom the foregoing descriptions. Such modifications and variations areintended to fall within the scope of the appended claims. The presenttechnology is to be limited only by the terms of the appended claims,along with the full scope of equivalents to which such claims areentitled. It is to be understood that this present technology is notlimited to particular methods, reagents, compounds compositions orbiological systems, which can, of course, vary. It is also to beunderstood that the terminology used herein is for the purpose ofdescribing particular embodiments only, and is not intended to belimiting.

1-16: (canceled) 17: An enclosure for monitoring an enclosed biologicalsubstance during a thawing process, the enclosure comprising: a bodydefining an interior volume configured to receive the enclosedbiological substance; an opening configured to allow transfer of theenclosed biological substance to and from the interior volume; a sensorcoupled to an interior facing wall of the body, the sensor configured tobe in direct contact with an exterior surface of the enclosed biologicalsubstance received within the interior volume, and to measure aphysiological and/or a physical parameter of the biological substanceduring the thawing process; and an RFID tag communicatively coupled tothe sensor. 18: The enclosure of claim 17, wherein the RFID tag isfacing in a direction opposite to the sensor. 19: The enclosure of claim17, wherein the sensor and the RFID tag are integrated into anelectronic device, and the electronic device is coupled to the interiorfacing wall of the body. 20: The enclosure of claim 17, wherein thesensor is a temperature sensor. 21: The enclosure of claim 18 furthercomprising a heat-nonconductive layer configured to inhibit thermalcommunication between the temperature sensor and ambient temperature.22: The enclosure of claim 17, wherein the enclosed biological substanceis a bag containing the biological substance. 23: The enclosure of claim17, wherein the enclosure is an overwrap bag. 24: The enclosure of claim17, wherein the enclosure is composed of a material having high thermalconductivity. 25: The enclosure of claim 17, wherein the interior volumeis sized to receive an enclosed biological substance having a volume of250 milliliters to 500 milliliters. 26: The enclosure of claim 17,wherein the enclosure is reversibly sealable. 27: The enclosure of claim17 further comprising an engaging mechanism at the opening. 28: A methodfor detecting or monitoring a physiological and/or a physical parameterof a biological substance during a thawing process, the methodcomprising: placing an enclosed biological substance in the enclosure ofclaim 17; acquiring data associated with the physical and/or thephysiological parameter of the biological substance during the thawingprocess using the sensor; and storing the acquired sensor data on theRFID tag. 29: The method of claim 28 further comprising communicatingthe stored data wirelessly to a RF reader. 30: The method of claim 28,wherein the biological substance is fresh, frozen, or thawed. 31: Themethod of claim 28, wherein the biological substance is selected fromthe group consisting of: medication, plasma, whole blood, glycerolizedblood, and RBCs. 32: The method of claim 28, wherein the physicalparameter of the biological substance is one or more of: identification,source history, demographic data, and time stamping. 33: The method ofclaim 28, wherein the physiological parameter of the biologicalsubstance is one or more of: temperature, pH, conductivity, glucose, O₂,and CO₂ levels. 34: The method of claim 28, wherein the sensor is atemperature sensor and the physiological and/or physical parameter ofthe biological substance is the temperature of the biological substance.35: The method claim 28, wherein the enclosed biological substance isplaced within the enclosure such that the sensor is in direct contactwith the exterior surface of the enclosed biological substance. 36: Amethod for detecting or monitoring a physiological and/or a physicalparameter of a biological substance in an enclosure during a thawingprocess, the method comprising: placing the enclosure containing thebiological substance within the body of a second enclosure; acquiringdata associated with the physical and/or the physiological parameter ofthe biological substance contained within the body of the secondenclosure during the thawing process using a sensor attached to aninterior facing wall of the body, wherein the sensor is in contact withan exterior surface of the enclosure containing the biologicalsubstance; storing the acquired sensor data on a RFID tag; andcommunicating the stored data wirelessly to a RF reader.